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Circulating tumor cell (CTC) surface antigens are a heterogeneous group of proteins and glycoproteins expressed on the plasma membrane of malignant cells that have entered the bloodstream from a primary tumor (NIH, 2025). These antigens, most notably the Epithelial Cell Adhesion Molecule (EpCAM), serve as the primary basis for the enrichment and detection of CTCs in liquid biopsy technologies like the FDA-approved CellSearch system (NIH, 2023). Beyond diagnostics, these surface markers are critical therapeutic targets for preventing metastasis, as they allow for the selective identification and elimination of disseminated tumor cells (NIH, 2025). Common antigens include growth factor receptors like HER2 and EGFR, as well as immune checkpoints like PD-L1, which can be targeted by monoclonal antibodies and antibody-drug conjugates (AACR, 2026). However, the dynamic nature of CTCs, particularly during epithelial-to-mesenchymal transition (EMT), often leads to the downregulation of epithelial markers and the emergence of mesenchymal antigens like vimentin or N-cadherin (NIH, 2025). This phenotypic plasticity poses a significant challenge for both capture-based diagnostics and targeted therapies, necessitating the use of multi-marker cocktails (TMC, 2026). Targeting these antigens aims to disrupt the metastatic cascade by neutralizing cells with high seeding potential before they can colonize distant organs (NIH, 2025).
Antibody-dependent cellular cytotoxicity (ADCC), complement-dependent cytotoxicity (CDC), inhibition of signaling pathways, and targeted delivery of cytotoxic agents via antibody-drug conjugates (ADCs).
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